A lesion is caused by any process that alters or damages tissue. A lesion can be defined as any pathological or traumatic discontinuity of tissue with partial loss of tissue function. The concept of a lesion includes wounds, sores, ulcers, tumors, cataracts and any other tissue damage. Lesions can range from the skin sores associated with eczema to the changes in lung tissue that occur in tuberculosis. Generally, a lesion can be characterized by the epithelium covering the underlying stromal connective tissue becoming fragile, leading to ulceration and bleeding.
Human papillomaviruses (HPV) are responsible for many cutaneous and mucosal lesions. Some viral genotypes are considered to be the causal agents of cervical cancer and oropharyngeal cancer. Natural genital HPV infection seems to be poorly immunogenic because of its nonproductive and non-inflammatory characteristics and also because of mechanisms developed by the virus to counteract the immune response. Human epithelial cells may be transformed by insinuation of the viral genome into the nucleus of the cells leading to immortalization of the cells, and neoplastic transformation which can lead to malignancy. Detection of these cellular changes is the aim of cancer screening tests such as the Papanicolaou Smear (Pap smear) of the cervix, which lead to follow up care where special illumination, magnification and the application of acetic acid can reveal visual evidence of cell proliferation. The goal is to find, target, biopsy and ultimately treat true cancer precursor lesions prior to malignant transformation and invasion.
Cervicovaginitis refers to inflammation of the squamous epithelium of the vagina and cervix caused by an inflammatory reaction to an infection. This damage leads to desquamation and ulceration, which can cause a reduction in the epithelial thickness due to loss of superficial and part of the intermediate layers of cells. In the deeper layers, the cells are swollen with infiltration of neutrophils in the intercellular space. The surface of the epithelium is covered by cellular debris and inflammatory mucopurulent secretions. The underlying connective tissue is congested with dilatation of the superficial vessels and with enlarged and dilated stromal papillae. Rare and uncommon cervical infections, due to tuberculosis, schistosomiasis and amoebiasis, cause extensive ulceration and necrosis of the cervix with symptoms and signs mimicking invasive cancer. Herpes simplex virus (HSV) can be present on the mucosal lining of the mouth or genitals. A large coalesced ulcer due to HSV can also mimic the appearance of invasive cancer. Chronic inflammation causing recurrent ulceration and healing of the cervix can result in a distortion of the cervix. Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis can be disseminated and some, e.g., C. neoformans, can result in pneumonia or meningitis. Longstanding viral, bacterial, fungal or protozoal infection and inflammation may lead to white or pink appearance as a result of fibrosis.
Previous devices to obtain a biopsy sample include brushes with rigid bristles that puncture and shear epithelial surfaces (U.S. Pat. No. 5,535,756 “Catheter with simultaneous brush cytology and scrape biopsy capability”, U.S. Pat. No. 6,258,044 “Apparatus and method for obtaining transepithelial specimen of a body surface using a non-lacerating technique”, U.S. Pat. No. 6,494,845 “Retractable brush for use with endoscope for brush biopsy” and U.S. Pat. No. 6,132,421 “Integrated epithelial removal tool”), single metal or plastic curettes that extend in a parallel direction to the applicator handle and are much larger than the innovation (U.S. Pat. No. 4,641,662 “Endocervical curette system” and U.S. Pat. No. 6,730,085 “Surgical biopsy instrument”), scalpels or similar bladed sharp cutting tools (U.S. Pat. No. 5,857,982 “Apparatus and method for removing tissue”, U.S. Pat. No. 5,800,362 “Cervical biopsy device”, U.S. Pat. No. 3,774,590 “Uterine Specimen Collecting Method”, U.S. Pat. No. 5,092,345 “Uterine cell sampler”, U.S. Pat. No. 4,061,146 “Tissue macerating instrument”, U.S. Pat. No. 5,868,668 “Surgical instrument”, U.S. Pat. No. 6,053,877 “Movable sample tube multiple biopsy sampling device”, U.S. Pat. No. 5,470,308 “Medical probe with biopsy stylet”, U.S. Pat. No. 7,137,956 “Endoscopic submucosal core biopsy device”, U.S. Pat. No. 4,168,698 “Endocervical strip biopsy instrument” and U.S. Pat. No. 4,757,826 “Endocervical biopsy instrument”; and U.S. publication No. 2005/0059905 “Tissue extraction and maceration device” and U.S. publication No. 2007/0093727 “Cervical tissue biopsy system and methods of use”), or very large electrified metal loops used to produce excisional biopsies (U.S. Pat. No. 5,913,857 “Methods and devices for collection of soft tissue” and U.S. Pat. No. 5,951,550 “Endocervical conization electrode apparatus”). One device performs simultaneous brush cytology and scrape biopsy on structures with an organic duct (U.S. Pat. No. 5,535,756, “Catheter with simultaneous brush cytology and scrape biopsy capability”). U.S. Pat. No. 5,643,307 “Colposcopic Biopsy Punch with Removable Multiple Sample Basket” has also been proposed to obtain biopsy samples when examining the cervix.
More recently, a number of non bristle biopsy collection devices which utilize a material (e.g., Kylon®) to obtain a biopsy sample from epithelial tissue have been proposed, including U.S. patent application Ser. No. 12/669,638 entitled “Frictional trans-epithelial tissue disruption and collection apparatus and method of inducing and/or augmenting an immune response”, which published as U.S. publication No. 20100210968 and Ser. No. 13/072,773 “Frictional trans-epithelial tissue disruption collection apparatus and method of inducing an immune response”, which published as U.S. publication No. 20110172557 and which are both explicitly incorporated by reference in their entireties.
Biopsy guides have been used to guide biopsy sampling tools into or onto lesions in the body that require radiological, sonographic, or magnetic resonance imaging, or an endoscopic portal such as a trochar or sheath to penetrate into the body or body cavity to access and accurately aim the active part of the device, usually a needle or cutting forceps tip. The goal of the existing biopsy guide technology has been to guide or target areas that are not easily accessible unless endoscopic or surgical access is provided to reach the target lesion. Biopsy guides are not used for epithelial lesions that are visually apparent outside the body such as skin, in a body cavity easily examined such as the oral cavity, or a body cavity that can be visualized with a speculum such as the vagina or anus.
Often the procedure for obtaining a biopsy sample is complicated when the epithelial tissue lies on an epithelial surface that is moist, wet or laden with mucous or other secretions. Often a biopsy is required of a specific lesion or inflamed region. In these situations, the medical professional will observe a specific location or target from which the biopsy can preferably be sampled. However, one or more procedures including applying, orienting, rotating with applied pressure, excision, obtaining sharp forceps samples with applied pressure and withdrawing the device from the desired specific location can be difficult. Depending on the nature of the epithelial tissue surface being sampled, the mechanical constraints can make these procedures challenging. The surface of female lower genital tract, anal, or oral epithelium may contain keratin or other proteinaceous material, and be coated with secretions from adjacent glands that may contain mucous or saliva. When a brush, fabric, metal forceps or curette is used to remove tissue from the area, the instrument can slide or slip away from a target lesion when pressure is applied to the sampling device, and the examiner can miss the area of concern, and instead sample adjacent “normal” appearing tissue instead. This can lead to examiner sampling error that can provide a false negative result, and missed detection.